BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients’ outcome

• Published in: British journal of cancer Vol. 102; no. 12; pp. 1762 - 1768
• Main Authors: Saridaki, Z, Papadatos-Pastos, D, Tzardi, M, Mavroudis, D, Bairaktari, E, Arvanity, H, Stathopoulos, E, Georgoulias, V, Souglakos, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.06.2010; Nature Publishing Group
• Subjects: 631/208/199; 631/208/737; 631/208/737/211/2120; 692/699/67/1504/1885; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Cyclin D1 - metabolism; Cyclin-dependent kinases; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Hospitals; Humans; Kinases; Male; Medical prognosis; Medical research; Metastasis; Microsatellite Instability; Middle Aged; Molecular Diagnostics; Molecular Medicine; Mutation; Neoplasm Metastasis; Oncology; Prognosis; Proteins; Proto-Oncogene Proteins B-raf - genetics; Tumors; Yeast; Greece; Crete; cyclin D1 expression; mutations; metastatic CRC; MSI status
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605694

Background: The significance of BRAF mutations, microsatelite instability (MSI) status and cyclin D1 expression in patients with metastatic colorectal cancer (mCRC) was evaluated. Methods: Primary tumours from 144 patients treated for mCRC were assessed for BRAF (V600E) mutation, MSI status and cyclin D1. The data were correlated with progression-free survival (PFS) and overall survival (OS). Results: BRAF mutations were detected in 10 (out of 22, 45%) patients with MSI-H tumours compared with 2 (out of 122, 1.6%) in those with microsatellite stable tumours ( P <0.001). The presence of BRAF mutations was correlated with cyclin D1 overexpression (7 out of 26 patients, 58% vs 5 out of 118 patients, 14%; P =0.001). Patients with BRAF -mutated primary tumours had a significantly decreased PFS (2.7 vs 9.8 months; P <0.001) and median OS (14 vs 30 months; P <0.001) than patients with wild-type (wt) tumours. Patients with MSI-H and BRAF -mutated tumours experienced significantly lower PFS (3.1 vs 11.4 months; P =0.008) and OS (14.5 vs 35.5 months; P =0.004) than patients with MSI-H and BRAF wt tumours. Similarly, BRAF mutations and cyclin D1 overexpression were correlated with decreased PFS (3.1 vs 8.6 months; P =0.03) and OS (17.8 vs 39.2 months; P =0.01). Conclusion: BRA F V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis.